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European Journal of Cancer (Oxford,... Jun 2024Frailty in newly-diagnosed multiple myeloma (NDMM) patients is associated with treatment-related toxicity, which negatively affects health-related quality of life...
BACKGROUND
Frailty in newly-diagnosed multiple myeloma (NDMM) patients is associated with treatment-related toxicity, which negatively affects health-related quality of life (HRQoL). Currently, data on changes in HRQoL of frail and intermediate-fit MM patients during active treatment and post-treatment follow-up are absent.
METHODS
The HOVON123 study (NTR4244) was a phase II trial in which NDMM patients ≥ 75 years were treated with nine dose-adjusted cycles of Melphalan-Prednisone-Bortezomib (MPV). Two HRQoL instruments (EORTC QLQ-C30 and -MY20) were obtained before start of treatment, after 3 and 9 months of treatment and 6 and 12 months after treatment for patients who did not yet start second-line treatment. HRQoL changes and/or differences in frail and intermediate-fit patients (IMWG frailty score) were reported only when both statistically significant (p < 0.005) and clinically relevant (>MID).
RESULTS
137 frail and 71 intermediate-fit patients were included in the analysis. Compliance was high and comparable in both groups. At baseline, frail patients reported lower global health status, lower physical functioning scores and more fatigue and pain compared to intermediate-fit patients. Both groups improved in global health status and future perspective; polyneuropathy complaints worsened over time. Frail patients improved over time in physical functioning, fatigue and pain. Improvement in global health status occurred earlier than in intermediate-fit patients.
CONCLUSION
HRQoL improved during anti-myeloma treatment in both intermediate-fit and frail MM patients. In frail patients, improvement occurred faster and, in more domains, which was retained during follow-up. This implies that physicians should not withhold safe and effective therapies from frail patients in fear of HRQoL deterioration.
PubMed: 38870747
DOI: 10.1016/j.ejca.2024.114153 -
Journal of Comparative Effectiveness... Jun 2024Eligibility criteria are pivotal in achieving clinical trial success, enabling targeted patient enrollment while ensuring the trial safety. However, overly restrictive...
Eligibility criteria are pivotal in achieving clinical trial success, enabling targeted patient enrollment while ensuring the trial safety. However, overly restrictive criteria hinder enrollment and study result generalizability. Broadening eligibility criteria enhances the trial inclusivity, diversity and enrollment pace. Liu proposed an AI pathfinder method leveraging real-world data to broaden criteria without compromising efficacy and safety outcomes, demonstrating promise in non-small cell lung cancer trials. To assess the robustness of the methodology, considering diverse qualities of real-world data and to promote its application. We revised the AI pathfinder method, applied it to relapsed and refractory multiple myeloma trials and compared it using two real-world data sources. We modified the assessment and considered a bootstrap confidence interval of the AI pathfinder to enhance the decision robustness. Our findings confirmed the AI pathfinder's potential in identifying certain eligibility criteria, in other words, prior complications and laboratory tests for relaxation or removal. However, a robust quantitative assessment, accounting for trial variability and real-world data quality, is crucial for confident decision-making and prioritizing safety alongside efficacy.
PubMed: 38869838
DOI: 10.57264/cer-2023-0164 -
Haematologica Jun 2024Not available.
Not available.
PubMed: 38867588
DOI: 10.3324/haematol.2024.285368 -
Clinical and Experimental Medicine Jun 2024Despite improvements in multiple myeloma (MM) survival rates, data on cardiovascular outcomes in long-term survivors remain lacking.
PURPOSE
Despite improvements in multiple myeloma (MM) survival rates, data on cardiovascular outcomes in long-term survivors remain lacking.
METHODS
This retrospective case-control study utilized the Korean National Health Insurance Service database (2009-2020) to compare the incidence of cardiovascular disease (CVD) between patients with MM and a matched control group, focusing on long-term (> 5 years) survivors. A preliminary case cohort (n = 15,402 patients with MM) and a matched control cohort (n = 123,216 patients without MM) were established based on birth year and sex. Following 1:1 propensity score matching, the final matched cohorts each comprised 15,402 participants.
RESULTS
The case and control cohorts were comparable in mean age (66.2 ± 11.5 years vs. 66.1 ± 11.3 years), sex, age distribution, and comorbidities. By the 8-year follow-up, the cumulative incidence of CV events (12.5% vs. 22.1%) and CVD risk were significantly lower in the case cohort. The 5-year landmark analysis revealed significant differences in CVD incidence between the cohorts (7.8% [case cohort] vs. 9.8% [control cohort]), with variations across age groups and sex, highlighting a significantly higher CVD risk among patients aged < 50 years in the case cohort (P < 0.001).
CONCLUSIONS
These findings underscore the need for vigilant CVD monitoring in MM long-term survivors, particularly those aged < 50 years at first diagnosis.
IMPLICATION FOR CANCER SURVIVORS
This study highlights the importance of integrating cardiovascular monitoring and risk management into long-term care for MM survivors, with a focus on younger patients and personalized interventions.
Topics: Humans; Multiple Myeloma; Male; Female; Aged; Middle Aged; Republic of Korea; Case-Control Studies; Cardiovascular Diseases; Retrospective Studies; Incidence; Cancer Survivors; Aged, 80 and over; Risk Factors; Adult
PubMed: 38864999
DOI: 10.1007/s10238-024-01368-2 -
Cancer Medicine Jun 2024Promising outcomes have been observed in multiple myeloma (MM) with the use of immunotherapies, specifically chimeric antigen receptor T (CAR-T) cell therapy. However, a...
BACKGROUND
Promising outcomes have been observed in multiple myeloma (MM) with the use of immunotherapies, specifically chimeric antigen receptor T (CAR-T) cell therapy. However, a portion of MM patients do not respond to CAR-T therapy, and the reasons for this lack of response remain unclear. The objective of this study was to investigate the impact of miR-34a on the immunosuppressive polarization of macrophages obtained from MM patients.
METHODS
The levels of miR-34a and TLR9 (Toll-like receptor 9) were examined in macrophages obtained from both healthy individuals and patients with MM. ELISA was employed to investigate the cytokine profiles of the macrophage samples. Co-culture experiments were conducted to evaluate the immunomodulatory impact of MM-associated macrophages on CAR-T cells.
RESULTS
There was an observed suppressed activation of macrophages and CD4 T lymphocytes in the blood samples of MM patients. Overexpression of miR-34a in MM-associated macrophages dampened the TLR9 expression and impaired the inflammatory polarization. In both the co-culture system and an animal model, MM-associated macrophages suppressed the activity and tumoricidal effect of CAR-T cells in a miR-34a-dependent manner.
CONCLUSION
The findings imply that targeting the macrophage miR-34a/TLR9 axis could potentially alleviate the immunosuppression associated with CAR-T therapy in MM patients.
Topics: Multiple Myeloma; MicroRNAs; Toll-Like Receptor 9; Humans; Animals; Mice; Signal Transduction; Coculture Techniques; Tumor-Associated Macrophages; Macrophages; Immunotherapy, Adoptive; Male; Female; Macrophage Activation; Cell Line, Tumor
PubMed: 38864479
DOI: 10.1002/cam4.7387 -
OTO Open 2024
PubMed: 38863484
DOI: 10.1002/oto2.144 -
Cell Communication and Signaling : CCS Jun 2024Multiple Myeloma (MM), a cancer of terminally differentiated plasma cells, is the second most prevalent hematological malignancy and is incurable due to the inevitable... (Review)
Review
Multiple Myeloma (MM), a cancer of terminally differentiated plasma cells, is the second most prevalent hematological malignancy and is incurable due to the inevitable development of drug resistance. Intense protein synthesis is a distinctive trait of MM cells, supporting the massive production of clonal immunoglobulins or free light chains. The mammalian target of rapamycin (mTOR) kinase is appreciated as a master regulator of vital cellular processes, including regulation of metabolism and protein synthesis, and can be found in two multiprotein complexes, mTORC1 and mTORC2. Dysregulation of these complexes is implicated in several types of cancer, including MM. Since mTOR has been shown to be aberrantly activated in a large portion of MM patients and to play a role in stimulating MM cell survival and resistance to several existing therapies, understanding the regulation and functions of the mTOR complexes is vital for the development of more effective therapeutic strategies. This review provides a general overview of the mTOR pathway, discussing key discoveries and recent insights related to the structure and regulation of mTOR complexes. Additionally, we highlight findings on the mechanisms by which mTOR is involved in protein synthesis and delve into mTOR-mediated processes occurring in MM. Finally, we summarize the progress and current challenges of drugs targeting mTOR complexes in MM.
Topics: Humans; Multiple Myeloma; TOR Serine-Threonine Kinases; Signal Transduction; Animals; Molecular Targeted Therapy; MTOR Inhibitors; Mechanistic Target of Rapamycin Complex 2
PubMed: 38862983
DOI: 10.1186/s12964-024-01699-3 -
Blood Cancer Journal Jun 2024
Topics: Humans; Multiple Myeloma; Neoplasm Staging; Female; Male; Middle Aged; Aged; Adult; Aged, 80 and over; Cohort Studies
PubMed: 38862493
DOI: 10.1038/s41408-024-01076-w -
Kansas Journal of Medicine 2024
PubMed: 38859988
DOI: 10.17161/kjm.vol17.21630